Pharmacokinetics of Ponazuril in Horses

Steady-state concentration of ponazuril can be readily achieved by using a loading dose.

1. Introduction

Ponazuril is a Food and Drug Administration–approved treatment for equine protozoal myeloencephalitis. In vitro studies have shown that concentrations of 100 μg/L of drug are needed in the cerebrospinal fluid (CSF) to kill the parasite Sarcocystis neurona. We predict that steady-state CSF concentrations of ponazuril can be reached by using a loading dose prior to the current label dose.

2. Materials and Methods

Eight adult horses with catheters in the jugular vein and lumbosacral subarachnoid space were administered a single dose of ponazuril at 5 mg/kg orally. Serum and CSF samples were collected for ponazuril concentration analysis beginning at day 0 (predose) through day 8. A one-compartment, open model with extravascular input and first-order elimination was fit to the serum and CSF raw data.

3. Results

The drug’s mean half-life was calculated at 38 hours. Approximately 1 week would be needed to reach steady-state concentrations without a loading dose. The modeling suggests that steady-state concentrations could be achieved immediately by using a loading dose of 15 mg/kg ponazuril. 

4. Discussion

Simulations using the pharmacokinetic model predict that a single loading dose of 15 mg/kg on day 1 can help achieve effective CSF concentrations after the first dose. The label dose should be used on the day after the loading dose and continued for 28 days. This treatment regimen may help stop S. neurona from inflicting damage to the central nervous system sooner than if the current label recommendations were followed.